Sexual Development and Behavior

  • Chromosomes

    • Male testes (gonads) produce sperm cells

    • Female ovaries (gonads) produce ova (eggs)

      • Sperm and ovum each have 23 chromosomes

    • Fertilization

      • Sperm cell + ovum = zygote

        • Dividing

      • 5 days later --> blastocyte

        • Far more divided mass of cells

          • When blastocyte merges with the uterus, it leads to an embryo

      • 10 weeks with differentiation of cells leads to a fetus

      • Total of 46 chromosomes

    • X and Y are sex chromosomes

      • Ova carry X, Sperm carry X or Y

        • XX = Female

        • XY = Male

      • Genotype

        • Based on genetics

      • Phenotype

        • Physical expression of genes

      • Biologically in humans, we are set up to develop into phenotypic females unless there is a trigger that shifts the genetic expression of different proteins

    • Sex-Determining Region of Y (SRY)

      • Testes Determining Factor (TDF)

    • Swyer Syndrome

      • 46, XY genotype

        • Prevalence approximately 1 in 80,000

          • (NIH estimate)

        • 15-20% SRY gene mutations or missing segment containing SRY gene

      • Results

        • Appearance is female (phenotype)

        • Can be intersex, spectrum of appearance

        • EXTREME CASES

          • Functional female genitals, vagina, uterus, and fallopian tubes

          • Genitals look female

          • Non functioning gonads

            • Streak gonads: straited, look very different

        • Typically raised female and report as female

      • Identified with puberty

        • Individuals are not able to start menstrual cycle

    • 46, XX Testicular Disorder

      • Translocation of genetic material between chromosomes

      • SRY gene is misplaced onto two X chromosomes

      • Prevalence approximately 1 in 25,000

        • (NIH estimate)

      • Results

        • Typically “normal” development of male genitalia

        •   Some affected individuals have ambiguous genitalia

        • Smaller testes and infertility

        • Typically raised as males and report male gender identity

        • Diagnosis can be made if testes do not descend, if not descended,
          they are removed

    • Differentiation occurs in the 2nd and 3rd trimesters

      • Primordial gonad

        • Can differentiate into male or female

          • Female (XX)

            • If no Y is presented, the cortex of the primordial gonad develops into ovary

          • Male (XY)

            • Under the influence of the Y chromosome, the medulla of the primordial gonad develops into testes

      • Ovaries will occur UNLESS testis determining factor is present

    • All fetuses have Mullerian Duct and Wolffian Ducts

      • Female ducts will develop on their own just like an ovary

        • Without hormonal input

      • Males need a substance to stop development and additional hormones to trigger development

      • Wolffian Ducts

        • Epididymis

          • Storing and matures sperm

        • Vas Deferens

          • Transports sperm

        • Seminal vesicles

          • Provide lubrication for sperm

        • Prostate

    • As testes develops

      • Mullerian-inhibiting substance and testosterone are synthesized and released

        • Chemical stops development of Mullerian system

        • Mullerian ducts will deteriorate and be absorbed by the body

      • 5-alpha reductase converts testosterone into dihydrotestosterone

        • Results

        • Mullerian system development is inhibited

        • Testosterone stimulates the development of the Wolffian system

        • Dihydrotestosterone stimulates the development of the external genitalia

        • 5-alpha-reductase Deficiency Syndrome

          • Guevedoces of Salinas

            • First identified by chemical missionaries

            • Individuals that started puberty transformed into a male

          • Lack sufficient levels of 5-alpha-reductase

            • Varying levels

            • Only needed during fetal development

            • Internalized testis

            • Wolffian system

            • External systems are not masculine

            • Puberty hits

              • High levels of testosterone produced

            • No conversion to dihydrotestosterone

            • Testosterone: genital development during puberty and into
              adulthood

            • Dihydrotesterone

              • Fetal development

    • Primary sex characteristics

      • Initial changes in development that are occurring in utero

      • Organizational effects of hormones

        • Ovaries vs testes

        • Mullerian vs wolffian

        • At birth

    • Secondary sex characteristics

      • Activation effects

      • With onset of puberty

      • Females

        • Widening of pelvis

        • Menstrual

        • Breasts

      • Males

        • Body hair

        • Broadening shoulders

        • Muscle development

  •  Are there differences between male and female brains?

    • Female Brains

      • Higher percentage of gray matter

      • Larger hippocampus

      • Larger ventral prefrontal cortex

        • Involved in social cognition and interpersonal judgement

      • Higher levels of serotonin, dopamine, and GABA

    • Male Brains

      • 10% larger cerebral hemispheres

      • Higher percentage of white matter and cerebral spinal fluid

      • Larger and more reactive amygdala

      • Larger hypothalamus

    • "Masculinization" of the [rodent] Brain

      • Testosterone is the hormone that is driving the changes

        • Changes occurring are the result of testosterone going from the testes, going through the blood brain barrier, to the CNS

      • Aromatase

        • Converts testosterone into estradiol

          • Estradiol is a type of estrogen

          • Happens both in the ovaries and the brain

      • Alpha Fetoprotein

        • Produced by placenta and fetal liver cells during fetal development

        • Binds to circulating estradiol and prevents its entry into the brain

          • Crosses the blood brain barrier and into the CNS

        • Does NOT bind to testosterone

        • Without, the estradiol COULD cross the blood brain barrier

        • Only produced up to 7 days after birth

          • Liver stops producing and after birth the placenta is gone

          • If detected after birth, something not good is happening in the body

      • Aromatization of Testosterone into Estradiol

 

  • Molecule of testosterone is in extracellular space

    • Makes its way into the cell neuron

  • Within the neuron, the testosterone is converted in Estradiol

  • Once estradiol is created, it makes its way into the nucleus

    • Estradiol binds to structures in the nucleus causing a cascade of changes

  • In order for this process to occur, you need to have higher levels of testosterone

    • Comes from the male developed testes and any testosterone the mother is producing

  • Any testosterone the female fetus produces and the mom produces  the same exact changes

    • Male fetuses produce a lo more testosterone

  • Case of John/Joan

    • John Money, Ph.D.

      • Controversial

      • John Money was developing and talking about a theory he had that biology does not
        matter in term of sexual development and identity

      • Believed it was all nurture, express as male or female because of how you are raised

      • You could take an infant and socialize to become male or female

      • Identical twin boys

        • One boy had penis destroyed by accidental circumcision

          • Bruce was now going to be raised as Brenda

          • Desperate mother did not know what to do, her child would not fit in

        • Dolls, dresses, female toys

        • Once a year, he (Dr. Money) collected data

■ Side note: ambiguous babies could, later on, have genitals altered to fit whichever gender

  • 2000/2001: word was out

  • John Money lied, he falsified data

■ Brenda changed back into a male identity, he had step children and was happily married

  • Dr. Money’s case study was a failure

    • When Brenda reaches puberty, they gave her female hormones there was
      too much male

    • At 5 years old he felt like he was in the wrong body

    • He was struggling so much his parents told him, within a month he
      changed back into a male

    • David’s brother committed suicide, he could not wrap mind around what
      had happened, David committed suicide at 38

  • WE CANNOT IGNORE BIOLOGY

  • Hypothalamic-Pituitary-Gonadal (HPG) Axis

    • Hypothalamus

      • Paraventricular nucleus and supraoptic nucleus directly release hormones through posterior pituitary portal

        • Such as oxytocin

          • Labeled the "love" hormone

          • Helps regulate bonding

            • Between mother and child

            • Between partners

              • Oxytocin levels rise during foreplay

              • Drives the bonding after sex

          • Helps further stimulate contractions

          • Stays activated during breastfeeding

        • Pitocin

          • If labor halts, drug given to mother's to induce labor

      • Releases hormones that stimulate anterior pituitary gonadotropin-releasing hormone

 

  • "Releasing" usually means it is coming from the hypothalamus

  • Anterior Pituitary

    • Releases gonadotropins

      • Follicle-stimulating hormone (FSH)

        • Ova development

        • Sperm development

        • Increase estradiol production

      • Luteinizing hormone (LH)

        • Stimulates testosterone secretion

          • From Leydig cells in testes

          • From Theca cells in ovaries

        • LH surge triggers ovulation

  • Gonadal hormones

    • Males and females produce all of these, the difference is the amount

    • Androgens

      • E.g., testosterone, hydrotestosterone 

      • Leydig cells in testes

      • Theca cells in ovaries

      • Responsible for masculinization of the male body:

        • Hair growth

        • Deepens voice

        • Bone density

        • Muscle mass

        • Sex drive

        • Further growth and development of the testes and the penis

      • In females:

        • Bone mass growth

        • Body hair growth

        • Sex drive

    • Estrogens

      • E.g., estradiol

      • Converted from testosterone by aromatase

      • In males:

        • Sperm maturity and sperm production

        • Plays a role in erections

      • In females:

        • Maturation in eggs

        • Thickening of the uterine wall

        • Lobito and sex drive

    • Gestagens

      • E.g., progesterone

      • Referred to as the pregnancy hormone

        • Initiates changes in the endometrium to allow for a developing zygotes to implant

        • Once implantation occurs progesterone is needed to keep placenta attached to the uterine wall

        • Prevents miscarriage and contractions

          • Maintains pregnancy

      • In males:

        • Not sure

        • Maybe plays a role in creation of sperm

        • Maybe acts as a chemical precursor to testosterone

  • Menstruation

    • Typical 28-day cycle

      • Days 1-5

        • Menstruation

      •  Day 6-14

        • Preovulatory

      • Day14

        • Ovulation

      • Day 14-28

        • Postovulatory

      • Lowest level

        • Changes occurring in uterus

        • Thickening of epithelial level of cells in uterus

      • Middle level

        • Ovary

        • Development of eggs (correspond with cycle)

          • Primary follicles

            • Immature, not yet viable

          • Secondary follicle

            • Matured, not viable

          • Graafian follicle

            • Fully mature egg

            • Can be fertilized and lead to pregnancy

          • Ovulation

            • Empty follicle

          • Corpus luteum

            • Dead, empty

            • Release of hormones

            • Stimulating and producing estradiol and testosterone still so
              that if an egg were to implant, pregnancy could begin

          • Corpus albicans

            • Last stage

            • No longer stimulating or producing hormones

            • Break down within ovary

      • Highest level

        • Hormone levels

        • FSH

          • Rises with onset on menstrual period

            • As the uterine wall is broken down and sheds

            • During this period, initiating maturation of primary follicle
              into secondary follicle

            • Increased level is now triggering an increased release of
              estradiol

        • Estrogen (estradiol)

          • Triggering last step of maturation

            • Secondary follicle -> Graafian follicle

          • Cells prepare for possible pregnancy

          • Cause pituitary to release FSH once more

          • FSH + estradiol = trigger of LH in pituitary release

          • Triggers LH

          • Secondary rise occurring at corpus luteum

        • LH

          • Causes mature graafian follicle to burst open

          • Ovulation

          • Once follicle bursts -> LH not needed

            • Burst follicle= corpus luteum

              • Triggers higher level release of estradiol from ovaries

        • If fertilization OCCURS

          • Egg is fertilized, implants into uterine wall

          • Post ovulatory

            • Walls have thickened and are easier for
              zygote to implant

          • Chemical signal is going to occur to maintain high levels of
            estradiol and progesterone

          • Corpus luteum is going to deteriorate and become corpus
            alibi cans

            • Now remainder of ovary is taking over

          • Progesterone is more important hormone to maintain
            pregnancy

            • If they were to drop the placenta will detach from uterine wall

              • Results in fetal death

                • Miscarriage

          • Oxytocin levels will rise and cause contractions

        • If fertilization DOES NOT OCCUR

          • The diagram is showing if it does not occur

          • Corpus luteum is producing estradiol

            • Egg is viable for up to four days

          • Uterus has to be prepared

            • Day 17 - 23

              • High estradiol

          • Triggering release of progesterone

            • Day 17 - 23

              • High progesterone

          • This rise thickens the uterus

            • Preparing for possible pregnancy

          • A about day 28

            • Stop triggering the release of estradiol and progesterone

              • Hormone levels are low

                • Triggers menstruation again

                  • Corpus luteum ---> corpus albicans

                • Cycle begins again

  • Birth Control Pills

    • Utilizes negative feedback loop between ovaries and the hypothalamus and pituitary

    • The most effective is the "combination pill"

      • Delivers both estrogen and progestin for 3 weeks

        • 4th week is placebo week

          • If one hormone fails to interfere, the other one increases the chances

    • May fail if cycle changes

      • Estrogen decreases secretion of FSH

        • Reduce the initial development of the egg

        • Even if it were to be released its too early for it to be fertilized

      • Progestin prevents secretion of LH

        • Delayed for a few days

        • Progesterone rise occurs post ovulation

          • Progestin signaling that you've already ovulated

            • Chemically the same thing

        • Prevents and interferes with LH release

          • Decreases the release of gonadal troponin releasing hormone from the hypothalamus

            • Start of cascade

          • Interfering with pituitary 

          • Reducing pulsing of hypothalamus releasing the hormone that gets cascade going

          • If the follicle never bursts or releases the egg, pregnancy CANNOT happen

    • This is a lot of hormones

    • Can mess with other things

  • Plan B

    • Levonorgestrel (progestin)

    • Taken within 72 hours of unprotected sex

      • Most effective within 24 hours

    • Stops release of ovum

      • Interfere with LH surge that may occur

      • Body is tricked into not responding because you're post ovulation

        • This stops LH release

    • If ovum is already released, may stop implantation?

      • Preventing another egg from implanting later

      • Prevents one pregnancy from starting after another one has already began

    • If fertilized ovum has implanted, this will not work

      • If anything, it will help the pregnancy

  • Mifepristone

    • Progesterone receptor blocker

      • Binds to progesterone and prevents progesterone from having its effect

        • Placenta will detach

      • Stop pregnancy from continuing

        • Up to 10 weeks

      • Use to end early pregnancy

        • Within 70 days or less since last menstrual period

      • Followed by misoprostol

        • 24 - 48 hours

        • Causes contraction so that the detached placenta will expel from the body

        • Softens and dilates cervix

        • Stimulated uterine contractions

  • Medial Preoptic Area

    • Nucleus within hypothalamus

    • Involved in regulation of male sexual behavior in rodents

      • Activity in medial preoptic area will lead to erection in male rodents --> intermission (copulation) --> ejaculation

        • Activity level starts to decrease

      • Damaged medial preoptic area

        • Rodents stopped engaging in sexual behavior

    • Highly impacted by testosterone

      • Seasonally rise

    • Mal pup is castrated and ass estrogen

      • Acts like female pup

    • Female pup ovaried are removed and is put on testosterone

      • Exhibits male pup behavior

  • Hormonal effects

    • Thought to be driven by pheromones

      • Lee-Boot Effect

        • When females are housed together without males present, cycles will eventually sync and they will stop ovulating and go into estress

          • Period of fertility that is not cyclic

        • If a male were introduced, estress would start up again

        • Does not happen in humans

      • Whitten Effect

        • Female cycles sync

        • Maybe happens in humans

        • Not clear

          • Seems that groups of females living together, reports of syncing up

      • Bruce Effect

        • In colonies of animals, where there is one dominant male

          • Dominant male has reproductive rights with the females

          • Females go through eustress and are fertile during certain times of the year

          • When another male challenges the paradominant male and the alpha fails, miscarriages are triggered in females

            • Soon after, they go back into eustress

          • Only in species that have alpha males

      • Vandenburgh Effect

        • Colonies of females living together

          • When a male is passing through, we see young females that are not sexually mature yet (prepubescent), the presence of the male will accelerate their sexual maturation

    • Ventromedial Nucleus (VMN of hypothalamus)

      • Involved in regulation of female sexual behaviors in rodents

        • Responds to estradiol and testosterone

        • During eustress enables a response to male presence

      • Stimulates arousal

        • Stays active until reproduction occurs

      • Lordosis

        • Mating posture

          • Arching back

          • Dropping shoulders

      • If not firing at a high rate, females can be aggressive